In our previous studies, we have used quantitative anatomical analyses of in vivo MR image volumes to characterize the regional distribution and severity of structural damage to the brain in different stages of the progression of HIV infection. Our results suggest that before clinical progression to AIDS, many HIV+ individuals are suffering from gradual degenerative changes in cerebral white matter and striatal gray matter, and that these changes accelerate in later stages of systemic disease progression. This volume loss in white matter and striatum results in increases in subarachnoid and ventricular CSF in patients with AIDS. These studies were carried out in subjects with only very limited substance abuse histories. Substance abusers may be at greater risk of structural damage to the brain associated with drug-induced ischemia or vasculitis, or to the CNS effects of metabolic and other needle-transmitted infectious illnesses; and therefore, HIV+ substance abusers may have significantly more CNS damage that HIV+ non-drug abusers. It seems likely that a pattern of drug-related pathology is superimposed upon that of HIV in the infected drug abusing population, however there are virtually no regional brain structural data at this time. The proposed studies would attempt to redress this problem by comparing the brains of matched groups of seropositive and seronegative methamphetamine dependent (METH+) sujects, and by comparing functionally (i.e., neuropsychologically) declining subjects, using quantitative MR anatomical methods that have been applied in the HNRC. The aims of this project are: 1) To characterize the brain morphological abnormalities present in HIV-/METH+ subjects relative to matched non-drug abusing (HIV- /METH-) controls, 2) To contrast the pattern of abnormalities observed in (HIV-/METH+) participants with that present in a matched group of HIV+/METH+ subjects; 3) To establish the degree to which worsening cognitive function in HIV+/METH+ subjects is associated with specific degenerative changes in the brain; and, 4) to relate in vivo anatommic changes derived from MR morphometry to postmortem analyses of neuronal and white matter injury.